Tourette Syndrome Deep Brain Stimulation: A Review and UpdatedRecommendations

Lauren E. Schrock, MD,1 Jonathan W. Mink, MD, PhD,2 Douglas W. Woods, PhD,3 Mauro Porta, MD,4 Dominico Servello, MD,5

Veerle Visser-Vandewalle, MD, PhD,6 Peter A. Silburn, MD,7 Thomas Foltynie, MRCP, PhD,8 Harrison C. Walker, MD,9

Joohi Shahed-Jimenez, MD,10 Rodolfo Savica, MD,1 Bryan T. Klassen, MD,11 Andre G. Machado, MD,12 Kelly D. Foote, MD,13

Jian-Guo Zhang, MD, PhD,14 Wei Hu, MD, PhD,11,14 Linda Ackermans, MD, PhD,15 Yasin Temel, MD, PhD,15

Zoltan Mari, MD,16 Barbara K. Changizi, MD,17 Andres Lozano, MD,18 M. Auyeung, MD,19 Takanobu Kaido, MD, PhD,20

Yves Agid, MD, PhD,21 Marie L. Welter, MD, PhD,22 Suketu M. Khandhar, MD,23 Alon G. Mogilner, MD, PhD,24

Michael H. Pourfar, MD,24 Benjamin L. Walter, MD,25 Jorge L. Juncos, MD,26 Robert E. Gross, MD,27 Jens Kuhn, MD,28

James F. Leckman, MD,29 Joseph A Neimat, MD,30 Michael S. Okun, MD,13* on behalf of theand Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group

1Department of Neurology, University of Utah, Salt Lake City, Utah, USA2Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA

3Department of Psychology, Texas A&M University, College Station, Texas, USA4Tourette Centre, IRCCS Galeazzi Hospital, Milan, Italy

5Functional Neurosurgical Unit, IRCCS Galeazzi Milano, Milan, Italy6Department of Stereotactic and Functional Neurosurgery, University of Cologne, Cologne, Germany

7Royal Brisbane and Women’s Hospital, School of Medicine, University of Queensland, Brisbane, Queensland, Australia8University College London Institute of Neurology, London, United Kingdom

9Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA10Department of Neurology, Baylor College of Medicine, Houston, Texas, USA

11Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA12Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA

13Departments of Neurology, Neurosurgery, and Psychiatry, University of Florida Center for Movement Disorders and Neurorestoration,

Gainesville, Florida, USA14Department of Neurosurgery, Beijing Tiantan Hospital, Capital University of Medical Sciences, Beijing, China

15Department of Neurosurgery, Maastricht University Medical Center, The Netherlands16Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA

17Departments of Neurology and Psychiatry, The Ohio State University Wexner Medical Center, Ohio, USA18Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada

19Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong, SAR China20Department of Neurosurgery, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan

21Institut du Cerveau et de la Moelle Epiniere (ICM), CHU Piti�e-Salpetriere, Paris, France22Centre de Recherche de l’Institut du Cerveau et de la Moelle �epiniere (CRICM), Universit�e Pierre et Marie Curie-Paris 6, Paris,

France23Northern California Kaiser Permanente, Surgical Movement Disorders Program, Sacramento, California, USA

24Departments of Neurosurgery and Neurology, New York University, Langone Medical Center, New York, New York, United States of

America25Movement Disorders Center, Neurological Institute, University Hospitals and Case Western Reserve University School of Medicine, South

Euclid, Ohio, USA26Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA

27Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia, USA28Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany

29Child Study Center and the Yale Center for Clinical Investigation, Yale University School of Medicine, New Haven, Connecticut, USA30Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA

------------------------------------------------------------------------------------------------------------------------------*Correspondence to: Michael S. Okun, MD, 3450 Hull Road, Department of Neurology, Center for Movement Disorders and Neurorestoration, Gaines-ville, FL 32607, E-mail: okun@neurology.ufl.edu

Funding agencies:

Relevant conflicts of interest/financial disclosures: Nothing to report.Author roles may be found in the online version of this article.

Received: 4 April 2014; Revised: 6 October 2014; Accepted: 8 October 2014

Published online 00 Month 2014 in Wiley Online Library(wileyonlinelibrary.com). DOI: 10.1002/mds.26094

R E V I E W

Movement Disorders, Vol. 00, No. 00, 2014 1

ABSTRACT: Deep brain stimulation (DBS) mayimprove disabling tics in severely affected medicationand behaviorally resistant Tourette syndrome (TS). Herewe review all reported cases of TS DBS and provideupdated recommendations for selection, assessment,and management of potential TS DBS cases based onthe literature and implantation experience. Candidatesshould have a Diagnostic and Statistical Manual of Men-tal Disorders, Fifth Edition (DSM V) diagnosis of TS withsevere motor and vocal tics, which despite exhaustivemedical and behavioral treatment trials result in signifi-cant impairment. Deep brain stimulation should beoffered to patients only by experienced DBS centersafter evaluation by a multidisciplinary team. Rigorouspreoperative and postoperative outcome measures oftics and associated comorbidities should be used. Ticsand comorbid neuropsychiatric conditions should beoptimally treated per current expert standards, and ticsshould be the major cause of disability. Psychogenictics, embellishment, and malingering should be recog-

nized and addressed. We have removed the previouslysuggested 25-year-old age limit, with the specificationthat a multidisciplinary team approach for screening isemployed. A local ethics committee or institutionalreview board should be consulted for consideration ofcases involving persons younger than 18 years of age,as well as in cases with urgent indications. Tourettesyndrome patients represent a unique and complexpopulation, and studies reveal a higher risk for post-DBS complications. Successes and failures have beenreported for multiple brain targets; however, the optimalsurgical approach remains unknown. Tourette syndromeDBS, though still evolving, is a promising approach fora subset of medication refractory and severely affectedpatients. VC 2014 International Parkinson and MovementDisorder Society

Key Words: Tourette syndrome; DBS; guidelines;deep brain stimulation

Tourette syndrome (TS) is a chronic neurodevelop-mental disorder characterized by motor and phonictics that by definition occur with a childhood onset.1

The syndrome is commonly associated with other neu-ropsychiatric comorbidities (eg, attention deficit hyper-activity disorder [ADHD], obsessive compulsivefeatures [OCD], and other behavioral manifestations).In most TS cases, the motor manifestations can bemanaged using TS education, comprehensive behav-ioral intervention for tics (CBIT), or a variety of medi-cations.2-4 The natural history of TS is that mostpatients will experience improvement of tics in lateadolescence or early adulthood.5,6 However, a subsetof patients will continue to experience disabling ticsdespite optimal medication and behavioral manage-ment. For severely affected patients, deep brain stimu-lation (DBS) has the potential to improve refractoryand disabling symptoms.

Methods

An experienced group of physicians participating inthe Tourette Syndrome Association (TSA) Interna-tional DBS Database/Registry, and also activelyinvolved in managing TS DBS patients, reviewed the2006 TSA guidelines7 and examined all reported casesof TS DBS. The TSA Database/Registry groupaccepted complete information sets on outcomes fromTS DBS (database entry), as well as registration ofcases performed with or without outcome information(registry entry). The group summarized the literature(Table 1) and based on their collective experience

with TS DBS provided suggested updates (Table 2)and a consensus opinion on the TSA recommendationsput in place in 2006.7

Literature Review

Deep brain stimulation is an established treatmentfor Parkinson’s disease (PD),8-12 essential tremor,13,14

dystonia,15-17 and obsessive-compulsive disorder,18,19

and has been granted either full Food and Drug Admin-istration (FDA) approval (PD, essential tremor), or ahumanitarian device exemption (FDA; dystonia, OCD)for each of these indications (in the United States).Many studies and position papers detail careful andmeticulous techniques for screening patients forDBS,13,16,20-22 including a few reports for TSpatients.23,24 General guidelines for selecting individualTS patients for DBS therapy and for managing thempreoperatively and postoperatively will have the poten-tial to improve risk–benefit ratios. The importance ofrigorous preoperative assessment, patient selection, DBSteam expertise and experience, as well as postoperativemanagement has been demonstrated previously, espe-cially when groups have studied cohorts of patientswho have failed DBS therapy.25,26 Because TS is achildhood-onset disorder, often with complex clinicalfeatures, a waxing and waning course, and frequentneuropsychiatric comorbidities, the evaluation ofpatients has a greater level of complexity than many ofthe other current DBS indications.In 2005, the TSA hosted a meeting of physicians

with experience and expertise in TS and DBS to

S C H R O C K E T A L

2 Movement Disorders, Vol. 00, No. 00, 2014

TABLE1.Review

ofreportedTSDBScases

Target:Thalamic

Study

Target

Sample

size

(n)

AgeatDBS

(years)

Subjects

<25

yrs

(ages)

Follo

w-up

Study

Design

Levelof

Evidence

Tic

Outcome

Measures

Comorbidity

OutcomeMeasures

SIB

WithIm

medi-

ate

RiskofBodily

Harm

(Yes/N

o)

Postoperative

LeadLocation

Reported(AC-P

C

Coordinates)

AdverseEvents

Reported

Servelloet

al.,

2008

61CM

-Pfc,Voa

18(15M

,3F)

17–47

8(2

�18

yrs)

3–18

mo

Case

series

IV1.YGTSS

64.7%

mean

improvem

ent

None

reported

Yes(9

with

SIB;

3cervicalmyelop-

athy,1disc

herniation,

2unableto

eat)

No1.

Transientstim-induced

vertigo

&visualAE

2.Poor

scalpincision

healingdueto

repetitive

touching;body

shield

required(n

51)

3.Abdominal

hematom

a(n

51)

4.Frequent

program-

mingrequiredinmany

Porta

etal.,

2009

58CM

-Pfc,Voa

15(12M

,3F);

*allprevi-

ously

reported6

2

17–46

7(2�18

yrs)

24mo

Case

series

IV1.

YGTSS

52%

mean

improvem

ent

1.Y-BO

CS31%

meanimprovem

ent

2.STAI

33%

meanimprovem

ent

3.BD

I26%

meanimprovem

ent

4.VASsubjectivesocial

impairm

ent

31%

meanimprovem

ent

Yes

No1.

3ptsfrom

previous

cohort(n

518)were

excluded:

2ptsrequestedremoval

ofIPGandDB

Swas

stopped

1pt

didpoorlyand

requiredsubsequent

GPi

DBS

Ackerm

ans

etal.,

2011

30

CM-Spv-Voi

8(2F,

6M);

*2Flostto

follow-up

21–48

1(21)

12mo

Double-blind

random

ized

cross-over

trial

36mo,

then

6moopen-

label

III1.

YGTSS

49%

improvem

ent

2.mRVTRS

35%

improvem

ent

1.Y-BO

CS—no

change

2.CA

ARS—

nochange

3.BD

I(Du

tch)—no

change

4.BA

I—no

change

5.VASforSIB—

nochange

Yes(1

life-

threatening,

lost

tofollow-up)

Yes

1.Decreasedenergy

lev-

els,subjectivegaze

dis-

turbance,negativeimpact

ondaily

livinginallpts

2.1sm

allhem

orrhageat

lead

tip—gaze

palsy3

6mo,

persistent

nystagmus

3.1IPGInfection

4.Severe

complications,

psychogenicsymptom

s,&

eventualdeathin1pt

lostto

follow-up(see

details

below40)

Duits

etal.,

2012

39CM

-Spv-Voi

1(F)*enrolled

butdidn’t

complete

previously

reported

trial31

211(21)

23mo

Case

report

IV1.

YGTSS—

worse

with

DBSON

:Pre-op—42

Stim

OFF—

12Stim

ON—39

1.Y-BO

CS:

Preop—

20Stim

OFF—

8Stim

ON—7

2.CA

ARS:

Pre-op—

58Stim

OFF—

42Stim

ON—45

Yes(life-

threatening)

No1.

Severe

postoperative

complications

with

psy-

chogenicparoxysm

alhypertonia,

disturbances

ofconsciousness,and

mutism

2.No

change

with

DBS

OFF

(Continued)

TABLE1.Continued

Target:Thalamic

Study

Target

Sample

size

(n)

AgeatDBS

(years)

Subjects

<25

yrs

(ages)

Follo

w-up

Study

Design

Levelof

Evidence

Tic

Outcome

Measures

Comorbidity

OutcomeMeasures

SIB

WithIm

medi-

ate

RiskofBodily

Harm

(Yes/N

o)

Postoperative

LeadLocation

Reported(AC-P

C

Coordinates)

AdverseEvents

Reported

3.BD

I-II:

Pre-op—

12Stim

OFF—

20Stim

ON—15

4.BA

IPre-op—32

Stim

OFF—

41Stim

ON—44

5.SIB(VAS)

Pre-op—

5.7

Stim

OFF—

0Stim

ON—8.9

3.Somatoform

disorder

identified

retrospectively

4.Pt

died

ofdehydration,

refusaltoeat/drink@3

yrspostoperatively

Ackerm

ans

2007

28CM

-Spv-Voi

1(M)*previ-

ously

reported3

1

390

6mo

case

report

IVNA

None

reported

Yes(head-

banging)

No1.

Hemorrhageat

distal

electrode

tip-->

verti-

calgazepalsy:subjec-

tiveworsening

with

DBSON

Ackerm

ans

etal.,

2006

27

CM-Spv-Voi

1(M)*prev

reported7

045

01yr

Case

report

IV1.

Videotaped

ticfre-

quency

(tics/min)by

2blindedraters

85%

reduction

1.PaduaInventory—

Revised(obsession-com

-pulsionrating)

62%

betterON

than

OFF

stim

NoNo

1.Decreasedenergy

level

2.Sexualdysfunction

Vandew

alle

etal.,

1999

68

CM-Spv-Voi

1(M)

420

4mo

Case

report

IV1.

Videotaped

ticfrequency

—Nearly100%

reduction(“except

for

someexcessiveeye

blinking”)

None

reported

NoNo

Notreported

Visser-Vande-

walleet

al.,

2003

70

CM-Spv-Voi

3(3M);*1M

previously

reported2

7

28,42,45

08mo—

5yrs

Case

series

IV1.

Videotaped

ticfre-

quency

(tics/10m

in)

—72%—90%

reduction

None

reported

No(burning

eye-

lashes

with

cig-

arettes,break-

ingglassin

hands)

No1.

Reducedenergy

levels

inall3

2.Sexualdysfunctionin2

pts

3.2ptseach

required3

revisionsof

IPGand

extensionwiresdueto

tractionpain

4.1pt

hadlower

scores

ontim

edtaskson

neuro-

psychologicaltesting

(Continued)

TABLE1.Continued

Target:Thalamic

Study

Target

Sample

size

(n)

AgeatDBS

(years)

Subjects

<25

yrs

(ages)

Follo

w-up

Study

Design

Levelof

Evidence

Tic

Outcome

Measures

Comorbidity

OutcomeMeasures

SIB

WithIm

medi-

ate

RiskofBodily

Harm

(Yes/N

o)

Postoperative

LeadLocation

Reported(AC-P

C

Coordinates)

AdverseEvents

Reported

Ackerm

ans

etal.,

2010

29

CM-Spv-Voi

2(2M);*previ-

ously

reported2

7,28

42,45

06–10

yrs

Case

reports

IV1.

Videotaped

ticfre-

quency

(tics/10m

in)

by3blindedraters

78%-92.6%

reduction

None

reported

No(breakingglass

inhands)

No1.

Reducedenergy

levels

inboth

pts

2.Both

with

hardware-

relatedcomplications

(tractionof

lead

inneck)

requiring

multiplesurgical

revisionsandlocalinjec-

tions

(previously

described

63)

3.Mild

visual

side

effects(vertigo,

blurry

vison)

inboth

4.Sexualdysfunctionin

both

5.Increasedaggression,

socialadaptationin1pt.

Maciunas

etal.,

2007

49

CM-Pf

5(4M,1F)

18–34

�1

4mo

Prospective

double-blind

crossovertrial;

four

7-d

random

ized

DBSconditions

R/L,

ON/OFF,

andopen-label

4-mofollow-up

III1.

mRVTRS

40%-67%

meanmotor

ticreduction

21%-70%

meanvocaltic

reduction

2.YGTSS

43.6%

mean

improvem

ent

2nonresponders

with

4.3–260.9%

ticexacerbation

3.TSSL

43%

meanreduction

1.SF-36(19%

mean

improvem

ent)

2.VAS(53%

meanimprovem

ent)

3.BD

I-2*(60%

meanimprovem

ent)

4.HA

M-D*(29%

meanimprovem

ent)

5.HA

M-A*(51%

meanimprovem

ent)

6.Y-BO

CS*(44%

meanimprovem

ent)

*Trend

toward

improvem

entat

4mo

Notreported

Yes(onlymean

coordinates

provided)

1.1pt

hadacutepsycho-

sison

day28

ofrandom

ized

phase—

thoughtto

berelatedto

acutelifestressors

Bajwaet

al.,

2007

31CM

-Spv-Voi

1(M)

480

2yrs

Case

report

IV1.YGTSS

63.6%

improvem

ent

1.Y-BO

CS72.4%

improvem

ent

2.CG

I“verymuchimproved”

Yes(head-snap-

ping

ticscaus-

ingcervical

myelopathy)

No1.

Although

ticsdram

ati-

cally

reduced,

the

head-snappingticshad

onlymild

reductionin

forcefulness

andhe

hadcontinuedneuro-

logicaldeterioration

dueto

myelopathy

(Continued)

TABLE1.Continued

Target:Thalamic

Study

Target

Sample

size

(n)

AgeatDBS

(years)

Subjects

<25

yrs

(ages)

Follo

w-up

Study

Design

Levelof

Evidence

Tic

Outcome

Measures

Comorbidity

OutcomeMeasures

SIB

WithIm

medi-

ate

RiskofBodily

Harm

(Yes/N

o)

Postoperative

LeadLocation

Reported(AC-P

C

Coordinates)

AdverseEvents

Reported

Shieldset

al.,

2008

67CM

*(ALIC

leadsprevi-

ously

removed)

1(F)

400

3mo

Case

report

IV1.

YGTSS

46%

improvem

ent

None

reported

Yes(head-snap-

ping

tics,lim

bfractures,

retinal

detachment)

No1.

High

stimulationset-

tings

requiredcausing

IPGdepletionq1–2

yrs

Savica

etal.,

2012

60CM

-Pf

3(2M,1F)

17–35

2(17,17)

1yr

Case

series

IV1.

YGTSS

70%

mean

improvem

ent

None

reported

Yes(jaw-

clenchingcaus-

ingdentalfrac-

tures;head-

snapping

tics)

No1.

Mild

stimulation-related

adverseeffectsam

ena-

bleto

programming

changes.

Idris

etal.,

2010

43CM

-Pf,Voa

1(M)

241

2mo

Case

report

IVNo

scales

reported

(tics

notedto

improve)

None

reported

NoNo

1.Postoperativebilateral

subcorticalhematom

asattributedto

lowfactor

XIIIA

Marceglia

etal.,

2010

50

CM-Pf,Voa

7(6M,1F)

*many/all

reported

elsewhere

(62)

24–52

1(24)

6mo-2yr

Case

series

IV1.

YGTSS

33%

meanimprove-

ment(10%

-49%

)

1.Y-BO

CS(3%

mean

improvem

ent;24%

improvem

entto

47%

worsening)

2.BD

I(7%

meanimprovem

ent)

3.STAI

(20%

meanimprovem

ent)

4.10-ptVAS

ofsocial

integration(14%

mean

improvem

ent

Notreported

NoNotreported

Servelloet

al.,

2010

63CM

-Pfc,Voa

(1unilateral,

excluded

from

analysis)

31(25M

,6F,);

*�18

previ-

ously

reported(62)

(4additional

ptsreceived

leadsin

multipletar-

gets&1in

ALIC/NA

only)

17–57

113mo-4yr

Case

series(36pt

cohort;

6excluded

from

analysisdueto

<3mof/u

ornon-thalam

ictarget)

IV1.

YGTSS

47%

meanimprove-

mentat

lastf/u

(p<

0.001)

1.Y-BO

CS17.3%

improvem

entat

lastf/u

(p5

.017)

2.BD

I32.4%

improvem

entat

lastf/u

(p<

0.001)

3.STAI

31.7%

improvem

entat

lastf/u

(p<

0.002)

4.10-ptVAS

ofsocial

integration

30.7%

improvem

entat

lastf/u

(p<

0.001)

Yes(2

with

cervi-

calm

yelopathy,

1with

col-

lapsed

trachea,

from

tics)

No1.

Infectionof

IPG/exten-

sionsrequiring

system

removal(n

51)

2.Infection

ofIPG

site

requiring

revision

(n5

2)3.

Wound

revision

along

lead

extensions

dueto

pickingbehavior

(n5

2)4.

Lead

revision

32in

1patient

5.Ruptureof

lead

exten-

sion

(n5

1)6.

IPGremoved

@27

mo

atpt

requestd

uetounsat-

isfactoryresults

1aes-

theticconcerns

(n5

1)

(Continued)

TABLE1.Continued

Target:Thalamic

Study

Target

Sample

size

(n)

AgeatDBS

(years)

Subjects

<25

yrs

(ages)

Follo

w-up

Study

Design

Levelof

Evidence

Tic

Outcome

Measures

Comorbidity

OutcomeMeasures

SIB

WithIm

medi-

ate

RiskofBodily

Harm

(Yes/N

o)

Postoperative

LeadLocation

Reported(AC-P

C

Coordinates)

AdverseEvents

Reported

7.DB

Sturned

offat

patient

request(n

52;

after2mo[excludedfrom

analysis]and2yr)

Porta

etal.,

2012

59CM

-Pfc,Voa

18(3F,

15M);

*previously

reported(62)

17–47

85–6yrs

Case

series

IV1.

YGTSS

73%

meanimprove-

ments(p

<0.001)

2.GC

I—ratings

variedbetweenpro-

viders

andbetween

provider

andpatients

1.Y-BO

CS42%

meanimprovem

ent

(p5

0.003)

(4pts

worsened)

2.STAI

46%

meanimprovem

ents

(p<

0.001)

3.BD

I55%

meanimprovem

ent

(p<

0.001)

Yes

No1.

Poor

wound

healing

dueto

patient

picking(n

51) 2.

Abdominal

wall

hematom

a3.

2ptsrequestedDB

Sturned

off@

3–4yrsfor

personalreasons

4.1pt

toldto

have

DBS

removed

dueto

repeated

infections

despite

improvem

entof

tics

5.Issues

with

noncom

pli-

ance

insomepatients

Kuhn

etal.,

2011

46Vop-Voa-Voi

(Unilateral)

227

(F);39

(M)

012

mo

Case

series

IV1.

YGTSS

75%-100%

improvem

ent

2.MRVRS

77%-100%

improvem

ent

1.BD

I-2—No

negative

impact

2.GA

F—Both

hadcontin-

uous

improvem

ent(52%

-73%)during12

mo

NoNo

1.Reducedverbalfluency

@1yr

inboth

pts

(�25%

worsening)

Leeet

al.,

2011

48CM

-Pf

131

(M)

018

mo

Case

report

IV1.

YGTSS

62%

improvem

ent@

6mo(sustained

at18

mo) 2.MRVRS

38%

improvem

ent

3.VAS

70%

improvem

ent

None

reported

Yes

No1.

None

reported;

pro-

gram

mingwas

reportedto

bedifficult

Okun

etal.,

2012

55CM

(scheduled

stimulation)

5(3F,

2M)

28–39

06mo

NIH-sponsored

clinicaltrials

planning

study

ofsafetyand

preliminaryeffi-

cacy;delayed

startactivation

(30d)

III1.

YGTSS

19%

mean

improvem

ent(p

5

0.01;5%

-30%

)2.

mRVTRS

36%

meanimprove-

ment(p

50.01)

1.Y-BO

CS2.

HDRS

3.YM

RS(Young

Mania

RatingScale

4.SF-36

5.QO

LAS

*Noneof

thesemeasures

improved,although

atrend

towardimproved

physicalfunctioning

inboth

QOLmeasures

Yes(3

of5pts)

Yes

1.No

major

adverse

events

(Continued)

TABLE1.Continued

Target:Thalamic

Study

Target

Sample

size

(n)

AgeatDBS

(years)

Subjects

<25

yrs

(ages)

Follo

w-up

Study

Design

Levelof

Evidence

Tic

Outcome

Measures

Comorbidity

OutcomeMeasures

SIB

WithIm

medi-

ate

RiskofBodily

Harm

(Yes/N

o)

Postoperative

LeadLocation

Reported(AC-P

C

Coordinates)

AdverseEvents

Reported

Kuhn

etal.,

2012

47Thalam

us,pal-

lidal,&nig-

ralinput

areas(uni-

lateralin1)

3(2M,1F);*2

previously

reported4

7,69

22–27

2(22,22)

NACase

series

IV1.

YGTSS

36%-83%

improvem

ent

None

reported

Notreported

Yes

None

reported

Vernaleken

etal.,

2009

69

Pf-DM-LM

1(M)

221

NACase

report

IV1.

YGTSS

36%

improvem

ent

None

reported

Notreported

Yes

1.Patient

hadpreviously

undergonebilateralG

PiDB

Swithout

improvem

ent

Servelloet

al.,

2011

64NA

39;*mostpre-

viously

reported(64)NA

NARetrospective

review

IVNotreported

Notreported

Notreported

Notreported

1.Lead

fracturedueto

head-snappingtics

2.18%

incidenceof

infectious

complications

(7patients),requiring

sur-

gicalrevision

3.All7

patientswith

infections

hadrecurrent

infection

4.Infections

thought

relatedto

compulsive

touching

ofsurgicalscars

Kaidoet

al.,

2011

44CM

-Pfc

3(1M,2F)

19–21

3(20,21,19)

12mo

Case

series

IV1.

YGTSS—

39.1%

mean

improvem

ent

1.Y-BO

CS—slight

decrease

in2pts,

increase

in1pt

2.BD

I-II—

variedbetween

patients

3.IQ—no

significant

meanchange

Yes(2

of3pts)

Notreported

1.Temporary

blurred

vision

with

increased

stimulationam

plitude

Motlagh

etal.,

2013

53Midline

thalam

ic4M

16–44

2(16,17)

6–95

mo

Case

series

IV1.

YGTSS—

dram

atic

improvem

ent

inthe2youngpts

(67%

-85%

);lim

itedimprove-

mentintheolder

pts(7%-20%

)

1.Y-BO

CS—100%

improvem

entin1pt;

minimalchange

orwor-

sening

intheothers

2.HD

RSandHA

RS—no

significant

change

Yes(2

of4pts)

Yes

1.44-yoM

hadcompul-

sive

pickingat

chestand

cranialincisions;DB

Ssystem

removed

because

ofinfection

2.42-yoM

hadDB

Ssys-

tem

removed

becauseof

lack

oftherapeutic

benefit

(Continued)

TABLE1.Continued

Target:Thalamic

Study

Target

Sample

size

(n)

AgeatDBS

(years)

Subjects

<25

yrs

(ages)

Follo

w-up

Study

Design

Levelof

Evidence

Tic

Outcome

Measures

Comorbidity

OutcomeMeasures

SIB

WithIm

medi-

ate

RiskofBodily

Harm

(Yes/N

o)

Postoperative

LeadLocation

Reported(AC-P

C

Coordinates)

AdverseEvents

Reported

Target:P

allidal

Diederich

etal.,

2005

36

pvGP

i1

27(M)

014

mo

Case

report

IV1.

Videotaped

ticfrequency

(tic/min)

85%

reduction

(66%

ticincrease

with

DBSOFF)

2.YGTSS

47.0%

improvem

ent

1.BD

I(75%

improvem

ent)

2.STAI

(30%

improvem

ent)

3.SR

SI-90-R

(31%

-61%

improvem

ent)

NoNo

1.Perm

anentleft-sided

bradykinesia(grade

2–3

onUPDR

S)—toleratedby

pt;reducedmildlywith

stimulationOFF3

48hr

2.Sm

allnon–m

ass-

occupyinghematom

a@

tipof

Relectrode

onpost-opMRI

3.Transientmild

fatigue

forseveralm

onths

Shahed

etal.,

2007

65pvGP

i1(M)*also

reported

(66)

161

6mo

Case

report

IV1.

YGTSS

84%

improvem

ent

2.TSSR

88%

improvem

ent

3.mRVTRS

21%

improvem

ent

1.Children’sY-BO

CS(69%

improvem

ent)

2.SF-36v2

(65%

improvem

ent)

3.BA

SC-2

(improvem

entsinseveral

domains,includinghyper-

activity,aggression,anxi-

ety,depression,

somatization)

NoNo

1.Patient

compulsively

pushed

onIPGs,requir-

ingbody

shieldfor4

wks

Shahed

etal.,

2007

66pvGP

i3

3M(16–35)

2(16,16)

3–12

mo

Case

series

IV1.

YGTSS

35%-76%

improvem

ent

2.TSSR

16%-90%

improvem

ent

3.RVTRS

17%-50%

improvem

ent

4.Ticfrequency

(tics/min)

37%-69%

reduction

1.Y-BO

CS(22%

-69%

improvem

ent)

Notreported

No1.

Nosurgicaladverse

events.

2.1patient

compulsively

pushed

ontheIPGsite.

(Continued)

TABLE1.Continued

Target:Thalamic

Study

Target

Sample

size

(n)

AgeatDBS

(years)

Subjects

<25

yrs

(ages)

Follo

w-up

Study

Design

Levelof

Evidence

Tic

Outcome

Measures

Comorbidity

OutcomeMeasures

SIB

WithIm

medi-

ate

RiskofBodily

Harm

(Yes/N

o)

Postoperative

LeadLocation

Reported(AC-P

C

Coordinates)

AdverseEvents

Reported

Dehninget

al.,

2008

34pvGP

i1

44(F)

012

mo

Case

report

IV1.

YGTSS

88%

improvem

ent;

noremaining

tics

None

reported

No(self-biting,

beating)

Yes

1.Frequent

visitsin1st

fewmonthsfordepres-

sion,vertigo,stom

ach

aches;difficulty

adjust-

ingto

newsituation

withouttics.

Dehninget

al.,

2011

35pvGP

i4;

*1previ-

ously

reported(35)3F

(25–44);

1M(38)

05–13

mo

Case

series

IV1.

YGTSS

6%worsening

to88%

improvem

ent

2.CG

I67%

meanimprove-

ment(including2with

nochange)

3.TSGS

12%

worsening

to80%

improvem

ent

(mean37%)

None

reported

Yes(burning

ofskinwith

iron)

No1.

Stimulationstopped

dueto

lack

ofresponse

(n5

2)2.

Lead

revision

toa

moreposteriorlocation

was

done

in1nonres-

ponder,without

improvem

ent

Dong

etal.,

2012

37pvGP

i(unilat-

eralR)

22M

(22,

41)

1(22)

1year

Case

report

IV1.

YGTSS

53%-59%

22reductionNo

nereported

NoNo

1.No

severe

adverse

effects

Dueck2009

38pvGP

i1

16(M)

1(16)

1year

Case

report

IV1.YGTSS(adapted

for

children;

inGer-

man)—

nosignifi-

cant

improvem

ent

Reportedno

associated

psychiatric

symptom

sNo

Yes

Notreported

Gallagher

2006

41pvGP

i1

26(M)

0NA

Case

report

IV“Disappearance

ofvocalticsand

markedimprove-

mentsinneck

movem

ents”

NANone

reported

NoNotreported

Martinez-Fer-

nandez

2011

52

pvGP

i(3);

amGP

i(3)

54M

(21–60);1F

(35)

1(21)

3–24

mo

Case

series

IV1.

YGTSS

29%

mean

improvem

ent

2.mRVTRS

45%

mean

improvem

ent

Impression:am

GPiis

superiorto

pvGP

i(YGTSS

38%

vs.20%

improvem

ent;

mRVTRS54%

vs.

37%)

1.Y-BO

CS(26%

mean

reduction)

2.GTS-QO

L(55%

mean

improvem

ent;availablein

3pts)

3.GTS-QO

LVAS—

40pointsmeanimprovem

ent

(total1

00)

Yes(2

with

cervical

myelopathy

from

head-

snapping

tics)

No1.

Twoinfections

in1

patient

(requiring

system

removal3

1,IPG/exten-

sionsremoval3

1)2.

Lethargy,agitation,

anxiety;unhappywith

results

despite

reduced

tics(n

51)

3.Low

thresholdcapsu-

larside

effects;lead

revi-

sion

toanteromedial

target,then

anxietywith

>100Hz

stimulation

(Continued)

TABLE1.Continued

Target:Thalamic

Study

Target

Sample

size

(n)

AgeatDBS

(years)

Subjects

<25

yrs

(ages)

Follo

w-up

Study

Design

Levelof

Evidence

Tic

Outcome

Measures

Comorbidity

OutcomeMeasures

SIB

WithIm

medi-

ate

RiskofBodily

Harm

(Yes/N

o)

Postoperative

LeadLocation

Reported(AC-P

C

Coordinates)

AdverseEvents

Reported

4.Acutedeteriorationin

ticswith

transient

stim

OFF—

only70%

ofprevi-

ouscontrolafterback

ON5.

Weightgain(n

51)

Cannon

etal.,

2012

33am

GPi

118M

(22–50);3F

(18–34)

2(18,22)

4–30

mo

Case

series

IV1.

YGTSS

50%

mean

reduction@

3mo

1.Y-BO

CS(59%

mean

improvem

ent)

2.HD

RS(74%

meanimprovem

ent)

3.GTS-QLS—

significant

improvem

ent(102%

meanimprovem

ent)

4.GA

F(57%

meanimprovem

ent)

Yes(requiring

24-

hrmonitoringto

preventhead

injury)

No1.

Onept

didnottolerate

DBSandturned

OFFafter

3mobecauseof

somatic

complaints

2.Hardwaremalfunction

(lead

fracture)

in3pts

(because

of:SIBtic,MVA,

unknow

n)3.

Lead

infectionrequir-

ingbilateralleadreplace-

ment(n

51)

4.Increasedanxietyin

2pts(1

transient,1persis-

tent,&fluctuating)

Filhoet

al.,

2007

56GP

e1

NANA

23mo

Case

report

(abstract

only)

IV1.

YGTSS—

81%

reduction

1.Y-BO

CS—84%

reduction

Notreported

NoNotreported

Piedimonte

etal.,

2013

57

GPe

147

(M)

02yrs

Case

report

IV1.

YGTSS

71%

improvem

ent@

6mo

significant

worsening

@2yr

whenIPGbat-

tery

died

1.Y-BO

CS(noOC

Dpre-

orpost-op)

2.HD

RS(82%

improvem

ent@

6mo)

3.HA

RS(75%

improvem

ent@

6mo)

4.GA

F—(36%

improvem

ent@

6mo)

NoNo

Notreported

Motlagh

etal.,

2013

53pvGP

i2

2M(24,

42)

1(24)

8–51

mo

Case

series

IV1.

YGTSS—

20%-44%

improvem

ent

1.Y-BO

CS—no

significant

change

2.HD

RS—no

change

tomild

improvem

ent

3.HA

RS—slight

improvem

ent

Yes(2

of2;

punching

self,

neck-snapping

tics1

cervical

spineinjury)

Yes

1.Lead

extender

revision

dueto

post-auricular

dis-

comfort,

possibleIPG

malfunctionwith

revision

toabdominalplacem

ent

2.Stimulation-induced

side

effects:hyperkinetic

leftarm

movem

ent,right

foot

cram

ping,flashingin

eyes,restlessness;Left

lead

quite

medial (Continued)

TABLE1.Continued

Target:Thalamic

Study

Target

Sample

size

(n)

AgeatDBS

(years)

Subjects

<25

yrs

(ages)

Follo

w-up

Study

Design

Levelof

Evidence

Tic

Outcome

Measures

Comorbidity

OutcomeMeasures

SIB

WithIm

medi-

ate

RiskofBodily

Harm

(Yes/N

o)

Postoperative

LeadLocation

Reported(AC-P

C

Coordinates)

AdverseEvents

Reported

Target:M

ultiple

Targets

Servelloet

al.,

2009

62CM

-Pfc,Voa

1ALIC/NA

(n5

1);

CM-Pfc,Voa

1ALIC/NA

add-on

(n5

2)

3;*Also

reported6

225–37(2M,

1F)

019–44moCase

series

(partof

4pt

cohort)

IV1.

YGTSS

2ptshad

modestreductionin

tics(23%

-34%

)afterinitialCM

-Pfc,VoaDB

Sbut

depression/OCD

remaineddisabling

83%

reductioninpt

with

simultaneous

CM-Pfc,Voa1

ALIC/NA

1.BD

I2.

STAI

3.YBOC

S4.

VASof

social

integration

2ptswith

“rescue”

ALIC/NAleadshadonly

mild

improvem

enton

thesemeasures

ptwith

simultaneousCM

-Pfc,Voa1

ALIC/NAdid

have

significant

improve-

ment(45%

,39%,61%,

35%,respectively)

Yes(1

cutself

with

knife,1

punchedselfin

head)

No1.

None

reported

2.ALIC/NArescue

leads

werenotvery

effective

Servelloet

al.,

2010

63pGPi

1ALIC/

NAadd-on

142

(F)

0pGPi:23

mo;

GPi

1ALIC/

NA

Case

series

(partof

36pt

cohort)

IV1.

YGTSS

14%

improvem

ent

@23

mowith

pGPi

41%

further

improvem

entafter

ALIC/NA(49%

total)

1.Y-BO

CS(26%

reductionwith

GPi;

16%

further

after

ALIC/NA)

2.STAI

(23%

improve-

mentwith

GPI;12%

fur-

ther

afterALIC/NA)

3.BD

I(5%

improvem

ent

with

GPi;30%

further

afterALIC/NA)

4.VASof

social

integra-

tion(15%

improvem

ent

with

GPi;12%

further

afterALIC/NA)

Notreported

forthiscase

No1.

Required“rescue”

ALIC/NAleadsbecause

ofsocialimpairm

ent

andpoor

QOLdespite

reductioninticswith

GPiD

BS

Ackerm

ans

etal.,

2006

27

pvGP

i1CM

-Spv-Voi

(*onlyGP

iactivated)

127

(M)

01yr

Case

report

(partof

2pt

series)

IV1.

Videotaped

exam

with

ticfrequency

(tics/min)by

2blindedraters

;93%

reduction

1.PI-R

forcompulsive

symptom

s—notedto

have

“totalresolution”

NoNo

1.Reducedenergy

level

2.Briefdystonicjerk

each

timeturned

ON

Welteret

al.,

2008

71CM

-Pf1

GPi

(limbic)

3;*1

previ-

ously

reported(43)2F

(36,

30);

1M(30)

020–60

mo

Controlled,

double-blind,

random

ized

crossover

study1

open

long-term

f/u

III1.

YGTSS

(cross-overperiod)

a)GP

i):65%-96%

improvem

ent

b)CM

-Pf

None

reported

Yes(eye

mutilation,

burningof

skin)

No1.

Thalam

ic—decreased

libidoin1pt

2.GP

i—lethargy

(3–4

d);

nausea

&vertigo

athigher

settings(n

52);

anxiety(n

51)

(Continued)

TABLE1.Continued

Target:Thalamic

Study

Target

Sample

size

(n)

AgeatDBS

(years)

Subjects

<25

yrs

(ages)

Follo

w-up

Study

Design

Levelof

Evidence

Tic

Outcome

Measures

Comorbidity

OutcomeMeasures

SIB

WithIm

medi-

ate

RiskofBodily

Harm

(Yes/N

o)

Postoperative

LeadLocation

Reported(AC-P

C

Coordinates)

AdverseEvents

Reported

30%-64%

improvem

ent

c)GP

i1CM

-Pf

43%-76%

improvem

ent

2.YGTSS(long-term

f/u)

CM-Pf/G

PiON

(n5

2;74%-82%

improvem

ent)

GPiON

(n5

1;mild

improvem

ent)

3.RVTRS

Houeto

etal.,

2005

42

CM-Pf1

GPi

(limbic)

136

(F)

011

mo

Prospective

double-blind

random

ized

N5

1crossover

trial

III1.

YGTSS

CM-Pf:64%

reduction

GPi:65%

reduction

“Sham”STIM:worse

than

baseline

CM-Pf1

GPi:34

(60%

reduction)

2.RVTRS

CM-Pf:77%

reduction

GPi:54%

reduction

“Sham”STIM:15%

reduction

CM-Pf1

GPi:77%

reduction

1.MAD

RS2.

BAS(anxiety)

3.BIS(im

pulsivity)

SUMMAR

Y:CM

-Pf:mood&

impulsivity

improved:SIB

resolved

GPi:mood&impulsivity

worse

than

CM-Pf;SIB

resolved

SHAM

:little

change

ofdepression/anxiety

CM-Pf1

GPi:SIB

resolved

Yes(eye

mutila-

tion,

burningof

skin)

No1.

Weightloss

(18kg

with

CM-Pf,continued

with

GPi)—

may

have

been

relatedto

with-

draw

alof

neuroleptics

2.Du

ringSH

AMstim:

SIB,

excoriations

atcables

Shields

etal.,

2008

67

ALIC/NA(*later

revisedto

CMDB

S)

140

(F)

018

mo

Case

report

IV1.

YGTSS

23%

improvem

ent

None

reported

Yes(head-snap-

ping

tics,lim

bfractures,retinal

detachment)

No1.

Lead

extensionfracture

dueto

residualhead-

snapping

ticsafterALIC/

NADB

S2.

Stimulation-induced

alteredmoodandimpulse

controlproblem

s2

48,19

(2M)

1(19)

Case

series

IV1.

YGTSS

Yes

1.48yoM:

(Continued)

TABLE1.Continued

Target:Thalamic

Study

Target

Sample

size

(n)

AgeatDBS

(years)

Subjects

<25

yrs

(ages)

Follo

w-up

Study

Design

Levelof

Evidence

Tic

Outcome

Measures

Comorbidity

OutcomeMeasures

SIB

WithIm

medi-

ate

RiskofBodily

Harm

(Yes/N

o)

Postoperative

LeadLocation

Reported(AC-P

C

Coordinates)

AdverseEvents

Reported

Motlagh

etal.,

2013

53

1.Midlinetha-

lamic1

pvGP

i2.

amGP

i1midlinetha-

lamic1

GPi-

pv

37–107

mo

19yo

with

3targetshadno

improvem

ent

48yo

had72%

improvem

ent

1.Y-BO

CS–48yo

had

significant

improvem

ent

(29-->

8);19yo

hadno

OCB

2.HD

RS–both

hadwor-

sening

ofdepression

3.HA

RS–no

change

Yes(2

of2;

slam

-mingforearm

againsthead,

head-snapping

tics1

cervical

injury;poking

lefteye,

left

cheekbiting)

2ndtarget

addeddueto

continuedhead-snapping

tics

GPileadextender

mal-

functiondueto

head-

snapping

tics

thalam

icandGP

ileads

nowOFF

2.19yoM:

ICU

hospitalization

with

sedationforworsening

tics2m

oafteram

GPi

placem

entto

preventeye

injury

3separate

DBSsurgeries

for3totalbilateraltargets

dueto

refractorytics;cur-

rentlyhasonlyRpvGP

ilead

onandno

improvem

ent

OtherTargets:ALIC/NA,

STN

Kuhn

etal.,

2007

45ALIC/NA

126

(M)

030

mo

Case

report

IV1.

YGTSS

41%

improvem

ent

2.mRVTRS

50%

improvem

ent

1.Y-BO

CS(52%

improvem

ent)

2.GA

F—significantly

improved

(7->

41)

Yes

No1.

High

stim

requirements

(2IPGreplacem

entsin30

mo) 2.

Temporary

deteriora-

tioninsymptom

swith

battery

depletion3

2Flaherty

etal.,

2005

40

ALIC/NA

137

(F)

018

mo

Case

report

IV1.

YGTSS

25%

improvem

ent\

2.Patient

ticlogs

45%

decrease

infrequency

and

severity

None

reported

Yes(head-snap-

ping

tics,lim

bfracture,

retinal

detachments)

No1.

Stim-induceddysarth-

ria,rhythm

icjaw

clenching

2.High-voltage

stim

inventralcontacts(near

NA)—

mild

apathy

and

depression;dorsalcon-

tactsinbody

ofcap-

sule—agitatedhypomania

(hrs

todays

onsetfor

moodeffects)

(Continued)

TABLE1.Continued

Target:Thalamic

Study

Target

Sample

size

(n)

AgeatDBS

(years)

Subjects

<25

yrs

(ages)

Follo

w-up

Study

Design

Levelof

Evidence

Tic

Outcome

Measures

Comorbidity

OutcomeMeasures

SIB

WithIm

medi-

ate

RiskofBodily

Harm

(Yes/N

o)

Postoperative

LeadLocation

Reported(AC-P

C

Coordinates)

AdverseEvents

Reported

3.IPGaccidentallyturned

offseveraltimes—symp-

tom

worsening

4.Fracturedlead

exten-

sion

requiring

replace-

ment—

dueto

tics

Zabek

etal.,

2008

72

ALIC/NA(uni-

lateralR

)1

31(M)

028

mo

Case

report

IV1.

15-m

invideotaped

exam

swith

ticcounts

80%

improvem

ent

None

reported

Yes(retinal

detachment,

blindness)

No1.

IPGmalfunctionat

9monthsdueto

RUE

motor

tics!

sxdeteri-

oration!

improve-

mentafterIPGreplaced

Neuner

etal.,

2009

54

ALIC/NA

138

(M)

036

mo

Case

report

IV1.

YGTSS

44%

improvem

ent

2.mRVTRS

58%

improvem

ents

1.Y-BO

CS(56%

reduction)

Yes(self-mutila-

tion;

breaking

glassinhands)

No1.

RapidIPGdepletion—

2IPGreplacem

entsin36

months

Burdick

etal.,

2010

32

ALIC/NA

133

(M)

030

mo

Case

report

IV1.

YGTSS

15%

worse

in1st6

mo

2.mRVTRS

Tics

20%

worse

@30

mo(5->

6)

1.Y-BO

CS(nosignificant

improvem

ent)

NoYes

Notreported

Martinez-

Torres

etal.,

2009

51

STN

138

(M)

01yr

Case

report

IV1.

RVTRS

97%

improvem

ent

1.UPDR

S(pthadPD

;57%

improvem

ent)

NoNo

Notreported

Servello

etal.,

2009

62

ALIC/NA

1;*Previously

reported(64)47

(M)

010

mo

Case

series(part

of4pt

cohort)

IV1.

YGTSS

79%

improvem

ent

1.Y-BO

CS(54%

improvem

ent)

2.BD

I(9%

improve-

ment;notsignificant)

3.STAI

(19%

improve-

ment;notsignificant)

4.10-ptVAS

ofsocial

integration(nochange)

NoNo

None

reported

BAS,BriefAnxiety

Scale;BIS,Barratt’s

ImpulsivityScale;CM-P

fc,Voa,centromediannucleus-parafascicular,andventro-oralis

complex;CM-S

pv-Voi,centromediannucleus-substantiaperiventricularis-nucleusventro-oralis

internus

complex;CM-P

f,centromediannucleus–parafascicularcomplex;Vop-Voa-Voi5

nucleusventro-oralis

posterior,ventro-oralis

anterior,andventro-oralis

internuscomplex;Pf-DM-LM,parafascicular,dorsomedialnucleus,andlamella

medialis;CM,centromediannucleusregion;GPi,globuspallidusinternus;pvGPi,posteroventralglobuspallidusinternus;amGPi,anteromedialglobuspallidusinternus;YGTSS,Yale

GlobalTic

Severity

RatingScale;Y-B

OCS,Yale-

BrownObsessiveCompulsiveScale;BDI,BeckDepressionInventory;BDI-2,BeckDepressionInventory,2ndEd.;HARS,HamiltonAnxiety

RatingScale;HDRS,HamiltonDepressionRatingScale;STA

I,State-TraitAnxiety

Inventory;

AC-P

C,anteriorcommissure–posteriorcommissure;mRVTRS,modifiedRushVideo-basedTic

RatingScale;RVTRS,RushVideo-based

Tic

RatingScale;CAARS,Conners

AdultADHD

RatingScale;PDD-S

Q,PervasiveDevelop-

mentalDisorder-SelfQuestionnaire;TSSL,To

uretteSyndromeSymptom

List;YMRS,YoungMania

RatingScale;QOLAS

5QualityofLifeAssessmentSchedule;SRSI-90-R

,Self-report

symptom

inventory

90Items—revised;TSSR

5Tic

Symptom

SelfReport;BASC-2,BehaviorAssessmentSystem

forChild

ren—2ndEd;TSGS,To

uretteSyndromeGlobalScale;PI-R,5

PaduaInventory

ofobsessivecompulsivedisordersymptoms—Revised.

develop recommendations, and these were publishedin 2006.7 Subsequently, a collaborative internationalnetwork of investigators was established, and in 2010to 2011 the TSA commissioned an International Data-base/Registry of DBS outcomes and cases performedin patients with a diagnosis of TS. The purpose of thispaper is to critically review the literature of all pub-lished cases of TS DBS and to provide updated opin-ions and recommendations for patient selection andassessment since 2006.7 Additionally, we aimed toencourage all clinicians and investigators who care forTS DBS patients to participate in the TSA DBS Data-base/Registry to collect more data and to enhance theunderstanding of surgical approaches and outcomes.Since 1999, 48 TS DBS studies have been published,

including approximately 120 patients from 23 centersin 13 countries. At least seven separate brain targetshave been employed27-72 (Table 1). The most com-monly used targets have been the medial thalamicregion targets (eg, centromedian nucleus–parafascicu-lar complex [CM-Pf]), with 70 reported cases. Thirty-one cases of pallidal TS DBS have been reported andhave included both anteromedial globus pallidus inter-nus (GPi; “limbic”) targets (n 5 14) and posteroven-

tral GPi targets (n 5 16). One case report of globuspallidus externa (GPe) DBS has also been published.The anterior limb of the internal capsule/nucleusaccumbens target in isolation has been used in six casereports, and one case of STN DBS has been reportedin a patient who had both tics and Parkinson’sdisease.Eleven reported cases have employed more than one

brain target (2 targets in 10 cases, and 1 case with 3brain targets). In most of these cases, however, theadditional target leads were added as “rescue” leadsbecause of inadequate response to the initial TS DBSleads. Three cases reported were part of a prospective,double-blind, randomized crossover study comparingthe CM-Pf and the anteromedial GPi targets.42,71

Although nearly all studies reported a beneficialeffect on tics, most of these reports were uncontrolledcases (n 5 100), and the results revealed wide varia-tions in study methods and outcomes, thus limitingmeaningful interpretation. Approximately one fifth ofthe papers did not report using a validated outcomeor videotape analysis. Rating scales to capture TScomorbidities (eg, obsessive-compulsive behavior, anx-iety) were used in fewer than one third of reported

TABLE 2. Updates to 2006 TS DBS Guidelines

2006 Guidelines Revised Guidelines

Diagnosis DSM-IV diagnosis of TS by expert clinician DSM-V diagnosis of TS by expert clinicianAgea �25 yrs 1. Age is not a strict criterion

2. Local ethics committee involvement for cases <18 years old

Tic severity 1.Severe tic disorder with functional impairment2. YGTSS > 35/503. Document with standardized video assessment

1. Severe tic disorder with functional impairment2. YGTSS > 35/503. Document with standardized video assessment

Neuropsychiatric comorbidities(ie, ADHD, OCB, depression, anxiety, etc.)

1. Tics should be the major symptom causingdisability2. Comorbid conditions should be stably treated3. Comorbid conditions should be assessed usingvalid rating scales when available

1. Tics should be the major symptom causingdisability2. Comorbid conditions should be stably treated3. Comorbid conditions should be assessed usingvalid rating scales when available

Failed conventional therapya 1. Failed treatment trials from 3 pharmacologicalclasses: a) alpha-adrenergic agonist, b) 2 dopamineagonists (typical & atypical), c) benzodiazepine2. Evaluated for suitability of behavioral interventionsfor tics

1. Failed treatment trials from 3 pharmacologicalclasses: a) alpha-adrenergic agonist, b) 2 dopamineagonists (typical & atypical), c) a drug from at leastone additional class (eg, clonazepam, tetrabenazine)2. A trial of CBIT should be offered

Comorbid medical disorders Stable for 6 months before DBS Stable for 6 months before DBSPsychosocial factors a 1. Adequate social support without acute or suba-

cute psychosocial stressors2. Active involvement with psychological interven-tions when necessary

1. Adequate social support without acute or suba-cute psychosocial stressors2. Active involvement with psychological interven-tions when necessary3. Caregiver available to accompany patient for fre-quent follow-up4. Psychogenic tics, embellishment, factitious symp-toms, personality disorders, and malingering mustbe recognized and addressed

Suicidal/homicidal ideation (SI/HI) a Not specifically addressed Documentation of no active SI/HI for 6 months

aRecommendations have changed since 2006.TS, Tourette syndrome; DBS, deep brain stimulation; DSM, Diagnostic and Statistical Manual of Mental Disorders; YGTSS, Yale Global Tic Severity Scale;ADHD, attention deficit hyperactivity disorder; OCB, obsessive compulsive behaviors; CBIT, cognitive behavioral intervention therapy.

S C H R O C K E T A L

16 Movement Disorders, Vol. 00, No. 00, 2014

studies, and postoperative DBS lead locations werereported in only 10 of 50 studies.Based on the levels of evidence classification scheme

that has been used by the American Academy of Neu-rology,73 only four of these 48 studies30,49,55,71 metcriteria for class III level of evidence (n 5 19),whereas the others were class IV. Given the smallnumber of patients and the use of multiple brain tar-gets within the class III studies, these data wouldlikely receive the lowest evidence rating (level U), indi-cating that the therapy remains unproven because ofinadequate or conflicting data.Since the last TSA guidelines were published in

2006,7 the field has gained important insight aboutsafety and the potential for specific adverse effects ofTS DBS. Thirty-three patients had TS DBS before theage of 25 years, including nine patients younger than18. The risk of surgical complications and adverseevents did not appear to be higher in these age groupswhen compared with patients older than 25 years.However, Servello et al.,61 in their series of 18patients who underwent bilateral CM-Pf DBS, cau-tioned that three of the four cases who were implantedbefore the age of 20 years had less than satisfactoryresults after 3 to 6 months of follow-up (significantspontaneous waxing and waning of symptoms requir-ing frequent DBS programming).Ackermans et al.30 reported substantial improve-

ment in six patients on the Yale Global Tic SeverityScale (YGTSS) between the ON and OFF stimulationconditions (37%), and also improvement after 6months of open-label therapy (49%) in a double-blindrandomized cross-over trial of centromedian nucleus–substantia periventricularis–nucleus ventro-oralis inter-nus (CM-Spv-Vo) DBS. Significant adverse effectswere reported, including decreased energy levels aswell as subjective gaze disturbances. One patient withcomorbid depression, pervasive developmental disor-der, compulsions, and severe self-injurious behavior(SIB) had surgery under the condition of clinicalurgency and had to be withdrawn from the trialbecause of severe postoperative complications withpsychogenic paroxysmal hypertonia, disturbances ofconsciousness, and mutism. Somatoform disorder inthis patient was only recognized retrospectively, andthe patient eventually died of dehydration after refus-ing intravenous fluids.39

Servello et al.64 has reported the most robust experi-ence with TS DBS, and also published an importantpaper analyzing the rates of infectious and hardware-related complications for different DBS indications(eg, PD, TS, tremor, and dystonia). Servello’s groupreported an increased risk of infectious complicationsin TS DBS (7 of 39 [18%] patients) compared with anoverall infection rate for all DBS indications of 3.7%(10 of 272 patients). The TS DBS patients also may be

at increased risk for hardware malfunction. Six casesof lead or lead extension fractures, or alternativelyIPG malfunction, have been reported,33,40,53,67,72 fourof which were attributed to residual head-snappingtics. These findings highlight the unique and poten-tially severe issues in the TS population. Whereas ticsthat are life threatening or carry significant risk ofimmediate bodily harm are observed in only 5.1% ofall TS patients, nearly 50 TS DBS cases with signifi-cant SIB have been reported in the literature, withmore than half of these cases involving a severe behav-ior or risk of severe bodily harm (eg, cervical myelop-athy from head-snapping tics, bone fractures, retinaldetachment).Although few data are available to guide postopera-

tive management of TS DBS patients, Servello et al.have the greatest experience with TS DBS to date.These authors have reported that TS DBS patientsrequire more frequent visits for DBS adjustments (ie,in excess of monthly visits stipulated in their protocol)than for other DBS indications, and also TS DBSpatients require substantial personal and family sup-port. For this reason, a thorough evaluation of thepatient’s adherence to recommendations, a clearassessment of the patient’s psychosocial situationinclusive of family dynamics, and the need for realisticpatient and family expectations should beemphasized.58,61,63

Given the dearth of double-blind controlled studiesof TS DBS, the lack of consistent outcome measuresrelated to TS comorbidities, and the lack of rigorousstudies comparing brain targets, few data are availableto guide target choice either in general or in specificpatients.Chronic continuous stimulation has been widely

assumed to be the only effective approach to TS DBS.Recently, however, this notion has been challenged byOkun et al.,55 who demonstrated the potential of non-continuous DBS paradigms in TS in a class III clinicaltrial planning study (n 5 5) of safety and preliminaryeffectiveness.55 Additionally, these authors have sug-gested that responsive approaches may be possible,especially by using oscillations (eg, the gamma band)and other brain network oscillations associated withDBS efficacy.74

Special Considerations Relevant toTS DBS and Guideline Updates

The official DSM V diagnostic criteria require thepresence of tics for more than a year, with onsetbefore the age of 18 years, and occurrence of bothmultiple motor and at least one phonic tic for a defini-tive diagnosis of TS.1 The variability (variability of tictypes, as well as the waxing and waning of tic sever-ity) in TS provides an extra level of complexity when

T O U R E T T E S Y N D R O M E D B S G U I D E L I N E S

Movement Disorders, Vol. 00, No. 00, 2014 17

considering TS candidates for DBS therapy. Tics canbe influenced by both environmental and psychologi-cal factors. Many TS patients can suppress tics par-tially or even completely for short periods, such aswhen being examined or when in public, but thenrelease tics when returning to a more comfortable set-ting. The recognition of embellishment, psychogenictics, factitious symptoms, personality disorders, andmalingering all need to be considered in the preopera-tive workup,39,75-77 similar to the experience in epi-lepsy surgery with nonepileptic events.78

A clinician with expertise and experience with TSpatients should confirm the diagnosis by strict criteria1

and address all psychological comorbidities and non-motor features before consideration of DBS. Patient-or family-expressed psychological “urgency” shouldnot heavily influence the clinician’s decision to proceedto an operation.79,80 All psychological and non-motorfeatures should be stabilized before consideration forsurgery. The evaluating team should be aware that theusual onset of TS occurs before the age of 10 yearsand has an average onset of 5.6 years. Tics typicallyfollow a waxing and waning course, and they peak inseverity in early adolescence. This peak is followed inmost cases by a gradual reduction in tic severity in lateadolescence and early adulthood.6,81 Longitudinalstudies have reported either complete remission oralternatively mild tics in early adulthood for more thantwo thirds of TS patients.5,6 Clinicians selecting DBScandidates would likely benefit from a list of predictivefactors that would facilitate identification of patientswho will remain severely affected into adulthood. Thisinformation is not currently known. Recent researchsuggests that tic severity, premonitory urges, and afamily history of TS may be childhood predictors of aworse health-related quality of life in adulthood.82

Although TS rarely causes severe disability, and gen-erally has a favorable prognosis, in a small subset ofpatients the symptoms cause severe disruption of inter-personal relationships, as well as impairments ofsocial, psychological, and intellectual development. Inextreme cases, TS may even become life threatening(eg, whiplash tics causing vertebral artery dissection83

or myelopathy84). This severe form of the syndrome isassociated with a higher rate of behavioral comorbid-ities (particularly OCD) and is more likely to berefractory to conservative medical management.Although malignant TS may affect only 5.1% of allTS patients, these cases will frequently come to theattention of TS DBS teams.85

The appropriate age to perform TS DBS isunknown and has been widely debated. In 2006, thefirst TSA guidelines7 proposed a minimum age crite-rion of 25 years to ensure that individuals who mightexperience spontaneous tic remission would not beimplanted with a surgical device. Since that time,

compelling arguments have been made for considera-tion of surgical intervention at younger ages in cer-tain cases of severe TS.86,87 The risk–benefit data forTS and for other DBS indications have shown thatthe actual DBS procedure is safe and well tolerated inchildren, particularly as demonstrated in those withdystonia.88 Because of increased evidence of a favor-able risk–benefit ratio for DBS in children with dysto-nia and TS, the age guideline has been adjusted bymost experts to recommend a multidisciplinary evalu-ation and discussion, without setting a firm age limit.Delaying surgery in younger incapacitated TSpatients could potentially result in irreparable harmto social, psychological, and intellectual development,even if the symptoms eventually subside with age.Similarly, in rare cases of “malignant tics” that occurin younger individuals, the tics themselves (eg, whip-lash tics) may carry greater risk for bodily harm,paralysis, or even death.A feature of TS with implications for determining

the efficacy of DBS is its frequent association with dis-abling psychiatric and behavioral comorbidities. Themost common of these are ADHD and OCD. Comor-bidities have a significant negative impact on the qual-ity of life in TS and can be a larger source ofimpairment when compared with motor tics.89,90 Iden-tification of comorbid psychiatric symptoms is criticalfor a DBS workup, because when left untreated, thesesymptoms may be the best predictors of a worse qual-ity of life, with or without DBS therapy.91 Comorbidsymptoms should be adequately treated before sur-gery, and patients should be informed that individualswho are deemed to be good candidates for DBS mayexperience a 30% to 50% or greater improvement inmotor tics. However, based on all available publishedcases, how DBS will impact TS comorbidities remainsunclear. Notably, comorbid OCD, ADHD, and moodissues have improved after DBS in some but not allcases.31,33,36,45,52,54,57,58,63,65,66

Deep brain stimulation should be offered to TSpatients only after evaluation by a multidisciplinary orinterdisciplinary team. This team should includeexperts in TS and associated comorbidities (ie, neurol-ogist, neurosurgeon, psychiatrist, neuropsychologist,DBS programmer [nurse or physician]). Centers per-forming DBS should have a high level of expertisewith DBS therapy, especially given the complexities ofthe TS patient. Potential therapy candidates should beindependently evaluated by each member of the team,and discussion of candidacy, risks, benefits, operativeapproach, and postoperative care should be pursuedbefore a decision on candidacy is reached.The ideal DBS candidate will have a DSM V diagno-

sis of TS and severe motor and vocal tics, whichdespite exhaustive medical and behavioral treatmenttrials result in significant impairment of self-esteem,

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18 Movement Disorders, Vol. 00, No. 00, 2014

social acceptance, family life, school or job functioning,or physical well-being. Psychosocial, medical, neurolog-ical, or psychiatric conditions that increase the risk ofthe procedure, preclude full participation in the opera-tion or post-DBS care, or that will potentially compro-mise the accurate assessment of outcomes should all beaddressed by the DBS multidisciplinary team beforesurgery. Tics and comorbid conditions should be opti-mally treated medically and behaviorally per currentexpert standards.3,9 Deep brain stimulation should notbe performed during periods of severe psychosocialinstability, which is likely to interfere with the closemonitoring and follow-up required. Psychosocial stressalso may increase the risk of suicide after surgery.92,93

In general, DBS surgery should be avoided if a patientis judged to be at imminent risk of suicide.80

Inclusion and Exclusion Criteria

A DSM V diagnosis of TS should be made by anexpert clinician who has experience in the evaluationand management of tic disorders (updated from DSMIV). Age should no longer be a strict criterion. Deepbrain stimulation should be considered only when allstandard medical and behavioral therapies have failedregardless of the patient’s age. Tourette syndromeDBS should rarely be an urgent indication, with thepossible exception of impending paralysis from head-snapping tics or profound SIB. A local ethics commit-tee or institutional review board should be consultedfor consideration of cases involving persons youngerthan 18 years of age, as well as in cases with urgentindications, particularly those with lower YGTSSscores or with shorter durations of symptoms.

TABLE 3. Pre- and post-operative outcome measures rec-ommended by the TSA*

Preoperative Information: Patient Assessment and SelectionAge, sex, ethnicityAge of TS onsetAge at diagnosis of TSAge at time of surgeryPsychiatric comorbidities (OCB, ADHD, depression, anxiety, SIB, other)TS medications tried and stopped bfore DBS (medication name, dose,and duration of trial)TS medications at the time of DBS (including dose)Documentation of CBIT being offered or of the trial and outcomeStandardized evaluation of tic type and severity (pre- and post-operatively)

Yale Global Tic Severity Score (YGTSS)Blinded video-based rating (e.g., Rush video scale rating of body

regions involved, tic severity and frequency)Premonitory Urge for Tics Scale 132

Clinical Global Impression (CGI for TS)Standardized evaluation of comorbid symptoms with valid and reliableinstruments when available (pre- and post-operatively)

Yale-Brown Obsessive Compulsive Scale (Y-BOCS)Conners’ Adult ADHD Rating Scale (CAARS)Depression: Beck Depression Inventory, 2nd Ed. (BDI-2), Hamilton

Depression Rating Scale (HDRS), Montgomery-Asberg Depression RatingScale (MADRS)

Anxiety: Hamilton Anxiety Rating Scale (HARS), State-Trait AnxietyInventory (STAI)

Mania: Young Mania Rating Scale (YMRS), K-SADS Mania RatingScale (MRS)

CGI (for ADHD and OCD)Suicide Assessment Scale (e.g., Columbia Suicide Severity Rating

Scale)Quality of Life Measurement (eg, Gilles-de-la-Tourette-Syndrome Qual-ity-of-Life scale [GTS-QOL], Global Assessment of Functioning scale[GAF], SF-36)

Surgical information: targeting and lead locationBrain target (eg, CM-Pfc-Voa thalamus, Gpi, ALIC/NA, other)Procedure (unilateral, bilateral, simultaneous, staged)Lead models and IPG models used (eg, Medtronic 3387/3389, ANS,Neuropace, primary cell, rechargeable, other)Lead location verification with postoperative MRI or CT (x-y-z coordi-nates of each contact in relation to the midcommissural point)

Postoperative information: programming, outcome data and adverse eventsStimulation parameters (active contacts, amplitude or current, fre-quency, pulse width, 6 impedence) at each follow-up visit and timeduration at that settingFrequency of programming adjustments (# to optimization, # per year)Stimulation-induced and general adverse effects

Psychiatric/cognitive (exacerbation of tics, mania, hypomania, cogni-tive decline, anxiety, OCB, depression, smile or laughter induction,impulsivity, psychosis, suicidal ideation/attempt, completed suicide,other)

General (paresthesias, muscle contractions, dyskinesias, bradykinesia,dystonia, dysarthria, stuttering, nausea or vertigo, lethargy, gait disorder,sexual side effects, weight loss/gain >10 pounds, death, other)Intraoperative or early surgical (1st post-op week) adverse events(symptomatic/asymptomatic hemorrhage, ischemic stroke, seizure, post-op confusion, infection, air embolism, DVT, death, other)Delayed surgical adverse events (infection of intracranial lead, extracra-nial lead/lead extender infection, infection of IPG, lead dislodgment, leadfracture, lead revision, suboptimally positioned lead, lead removal, IPGremoval, other)Timing of IPG replacement or need for recharging

(Continued)

Regular postoperative evaluations to include standardized rating scalesof TS and co-morbidities

YGTSSBlinded video-based ratingY-BOCSPremonitory Urge for Tics Scale (PUTS) 132

Conner’s ADHD ScaleDepression: BDI-2, HDRS or MADRSAnxiety: HARS, STAIMania: YMRS, K-SADS, MRSCGISuicide Assessment Scale (eg, Columbia Suicide Severity Rating

Scale)

a The exact measures are less important than the adherence to measure-ment of pre/post outcomes in each of the major domains (motor, non-motor, mood, quality of life).TSA, Tourette Syndrome Association; TS, Tourette syndrome; OCB, obses-sive compulsive behaviors; ADHD, attention deficit hyperactivity disorder;SIB, self-injurious behavior; DBS, deep brain stimulation; CBIT, cognitivebehavioral intervention therapy; K-SADS, kiddie schedule for affective dis-orders and schizophrenia; OCD, obsessive-compulsive disorder; SF-36,short form health surgery 36; CM-Pfc-Voa, centromedian nucleus-parafas-cicular complex; Gpi, globus pallipus internus; ALIC/NA, anterior limb ofthe internal capsule/nucleus accumbens; IPG, implantable—pulse genera-tor; MRI, magnetic resonance imaging; CT, computed tomography; DVT,deep venus thrombosis.

T O U R E T T E S Y N D R O M E D B S G U I D E L I N E S

Movement Disorders, Vol. 00, No. 00, 2014 19

The candidate should have a chronic and severe ticdisorder with severe functional impairment. A standar-dized videotape assessment (eg, Rush Video-Based TicRating Scale94) and a validated rating scale (eg, YaleGlobal Tic Severity Scale [YGTSS]95) should be usedto document tic severity. In most cases the TS patientshould have a total YGTSS score greater than 35/50documented over the course of a year.Motor or vocal tics should be the primary symp-

tom causing disability for a patient. Although mostcandidates are likely to have comorbid ADHD,OCD, depression, anxiety, or other non-motor symp-toms, these symptoms should be adequately treatedand stable for a minimum of 6 months and shouldnot be the major source of functional impairment. Insome patients, the commonly noted comorbidity ofSIB, particularly severe SIB,96 may be inextricablyintertwined with tics, and thus may be a primarycontributor to disability. Patients with SIB or pickingbehavior should be warned preoperatively of anincreased risk of infection or hardware-relatedcomplications.64

At a minimum, documentation of unsuccessful treat-ment trials is needed from three pharmacologicalclasses: (1) an alpha-adrenergic agonist, (2) two dopa-mine antagonists (including one typical and one atypi-cal), and (3) a drug from at least one additional class(e.g., clonazepam, topiramate, or tetrabenazine). Tet-

rabenazine should be tried if accessible.97,98 In addi-tion, CBIT delivered by a trained CBIT therapistshould be offered,2,4 and the patient must have dem-onstrated his or her ability to adhere to recommendedtreatment plans before serious surgical consideration.Unfortunately, in many locations, including some cen-ters experienced with TS, substantial issues of access,wait times, and lack of insurance reimbursement maketherapies such as CBIT not always feasible, particu-larly in cases of malignant TS.The neuropsychological profile must indicate that the

candidate will be well suited to tolerate the surgical proce-dure, rigorous postoperative follow-up, and the possibilityof both a negative or positive outcome.87 The potential forprogressive cognitive impairment should be absent on thisprofile, or a follow-up profile should be performed to con-firm findings and to also track progression.Because of the substantial time commitment

required for optimization of DBS therapy, as well asthe significant impact that psychosocial factors canhave on the disorder, any candidate for TS DBS musthave adequate social support, and there should not beacute or subacute psychosocial stressors. A caregivermust be available to accompany the patient for visitsand for frequent programming.Similar to that proposed in the previous guidelines,

there should be documentation of no suicidal idea-tion and no psychiatric hospitalization for 6 monthsbefore surgery. Depression and mood disorders mustbe stable and treated. Preferably suicidal tendencyshould be monitored preoperatively and postopera-tively with a scale such as the Columbia SuicideScale99 or another similar measure. Active or recentdependence on drugs or alcohol are contraindicationsfor surgery. No structural lesions should be seen onmagnetic resonance imaging that are deemed to pres-ent a significant risk by the neurosurgeon, nor medi-cal, neurological, or cognitive disorders that wouldsignificantly increase the risk of a failed procedure,surgical complications, or interfere with postopera-tive management. A new criterion employed by mostcenters involved with TS DBS since 2006 is that anexpert clinician should feel comfortable that malin-gering, factitious disorder, or psychogenic tics are notpresent.Teams implanting TS patients should record preop-

erative and postoperative outcome measures, includingage, disease duration, tic subtypes, motor, mood,behavior, quality of life, medications, postoperativelead locations, stimulation settings, and suicidal ten-dencies. Validated clinical rating scales of tics and TScomorbidities are critical. A full list of the measuresrecommended by the TSA and employed in in theInternational TSA DBS Database/Registry is providedin Table 3. The exact measures are less importantthan the adherence to measurement of preoperative

TABLE 4. TS DBS Inclusion and Exclusion Criteria

Inclusion Criteria Exclusion Criteria

1. DSM-V Diagnosis of TS by expertclinician2. Age is not a strict criterion. Localethics committee involvement forcases involving persons < 18 years,and for cases considered “urgent”(eg, impending paralysis from head-snapping tics)3. Tic Severity: YGTSS >35/504. Tics are primary cause ofdisability5. Tics are refractory to conservativetherapy (failed trials of medicationsfrom 3 classes, CBIT offered)6. Co-morbid medical, neurological,

and psychiatric disorders are treatedand stable 3 6 months7. Psychosocial environment is stable8. Demonstrated ability to adhere torecommended treatments9. Neuropsychological profile indi-cates candidate can toleratedemands of surgery, postoperativefollow-up, and possibility of pooroutcome

1. Active suicidal or homicidalideation within 6 months2. Active or recent substanceabuse3. Structural lesions on brainMRI4. Medical, neurological, orpsychiatric disorders thatincrease the risk of a failedprocedure or interferencewith postoperativemanagement5. Malingering, factitious dis-order, or psychogenic tics

TS, Tourette syndrome; DBS, deep brain stimulation; DSM-V, Diagnosticand Statistical Manual of Mental Disorders; YGTSS, Yale Global Tic Sever-ity Scale; CBIT, cognitive behavioral intervention therapy.

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20 Movement Disorders, Vol. 00, No. 00, 2014

and postoperative outcomes in each of the majordomains (motor, non-motor, mood, quality of life).

Discussion

The centers participating in the TSA InternationalDatabase/Registry have employed several importantpractice pattern changes to the selection and assess-ment recommendations for the use of TS DBS. These

changes were based on the expanded experience in thefield since the 2006 guidelines. The changes and partic-ularly the inclusion criteria (Table 4) reflect the grow-ing experience with more than 120 cases reportedworldwide. In particular, the relative safety of the pro-cedure has been better established. Additionally, someTS cases may be appropriate for DBS before the previ-ously recommended age of 25 years. Most centers nowemploy a multidisciplinary team approach for screeningrather than an age limit. For patients younger than age

FIG. 1. Flow diagram of recommended DBS evaluation process for TS.

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18, one should have additional institutional approval.Centers performing TS DBS should use preoperativeand postoperative outcome measures, regardless ofwhether they adopt the TS DBS Database/Registryguidelines. All patients undergoing TS DBS should beaware that there is a reasonable chance for motor andvocal tic improvement, but that other co-morbidities ingeneral respond less consistently to therapy. Cliniciansshould educate patients and families on the increasedinfection rate, and the potential for increasedhardware-related issues. Figure 1 provides a diagram ofthe recommended evaluation before TS DBS.The most appropriate brain target for an individual

symptom profile remains unknown. The consensus ofthe centers implanting TS DBS includes the following:(1) all adverse events, whether major or minor, surgi-cal or nonsurgical, related or unrelated to the therapy,should be recorded and reported; (2) detailed descrip-tions of all surgical and programming proceduresshould be recorded; and (3) preoperative and postop-erative targeting should be reported, because wherethe optimal target regions are located, even within tar-gets, remains unclear. Psychological issues should bescreened preoperatively and monitored postopera-tively. Finally, rigorous reporting of DBS failures andadverse events is needed.100 Databases and registriesmay be our best hope of advancing the field quickly,because most expert centers will do less than a hand-ful of TS surgeries.After an extensive review of the literature and con-

sensus among implanters of DBS, we conclude that TSDBS, though still evolving, is a promising approachfor a subset of medication-refractory and severelyaffected patients.

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